miR-10b Downregulated by DNA Methylation Acts as a Tumor Suppressor in HPV-Positive Cervical Cancer via Targeting Tiam1

Yu, Miaomei; Xu, Yun; Pan, Lili; Feng, Yuehua; Luo, Kaiming; Mu, Qinfeng; Luo, Guopei

doi:10.1159/000495680

Cited by 27 publications

(21 citation statements)

References 13 publications

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“…[41] Consistently, many studies implied that Tiam1 overexpression exhibited an accelerative effect in regulating malignant cell proliferation in a wide range of cancers, including hepatocellular carcinoma, [42–44] oral cancer, [45] lung cancer, [35] esophageal cancer, [46,47] pancreatic cancer, [13,48] ovarian cancer, [49] cervical cancer, [33,50] colon cancer, [51–54] gastric cancer, [55] osteosarcoma, [56,57] nasopharyngeal cancer, [14] laryngeal cancer, [31] and cholangiocarcinoma. [58] Besides, lots of studies indicated that upregulation of Tiam1 could protect malignant cells from apoptotic death in esophageal cancer, [46,47] cervical cancer, [50] laryngeal cancer, [31] retinoblastoma, [59] and colon cancer. [54] Third, a few recent studies demonstrated that Tiam1 was able to promote of angiogenesis cervical [33] and lung cancer.…”

Section: Discussionmentioning

confidence: 91%

Tiam1 high expression is associated with poor prognosis in solid cancers

Ding

Yang²,

Wang³

2019

Medicine

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Background: A number of studies have attempted to determine the prognostic value of T-cell lymphoma invasion and metastasis-inducing factor 1 (Tiam1) in patients with solid cancers, but the reported results were of inconsistency. Thus, we performed a systematic review and meta-analysis to exhaustively evaluate the prognostic role of Tiam1 expression in patients with solid cancers.Methods: We retrieved literature published in between 1994 and April 22th, 2019 through searching PubMed, Web of Science and China national knowledge infrastructure (CNKI). Hazard ratios (HRs) coupled with 95% confidence intervals (95% CIs) were used to assess the relationship of Tiam1 expression and overall survival (OS), and disease-free survival (DFS).Results: A total of 2647 patients with solid cancers in 20 studies were enrolled in our meta-analysis eventually. The pooled results showed that Tiam1 high expression was closely correlated with poor OS (HR = 2.17, 95% CI: 1.80–2.61, P = .000) and DFS (pooled HR = 1.95, 95% CI = 1.58–2.40, P = .000). Moreover, our subgroup analysis and sensitivity analysis demonstrated the reliability and stability of our pooled results.Conclusion: In conclusion, this meta-analysis confirmed that Tiam1 higher expression positively correlated with OS and DFS, suggesting that Tiam1 may act as a valuable prognostic predictor and therapeutic target for patients with solid cancers. Nevertheless, in future more homogeneous and prospective studies should be performed to further support our findings.

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Section: Discussionmentioning

confidence: 91%

Tiam1 high expression is associated with poor prognosis in solid cancers

Ding

Yang²,

Wang³

2019

Medicine

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“…The stable expression of these two miRNAs inhibited Rac activation, cell growth, migration and invasion, as well as induced apoptosis by regulating TIAM1 expression. Furthermore, these results translated to mice as the expressions of miR-10a and miR-10b were found to reduce tumor growth and metastasis in esophageal squamous cell carcinoma [391] and cervical cancer [393], respectively. It was found that miR-10b was epigenetically silenced by DNA methylation [393,394], suggesting that demethylating agents could reactivate tumor suppressors to combat cancer progression.…”

Section: Mirna Targeting Of Rhogefsmentioning

confidence: 91%

“…Although originally identified as a Rac-specific GEF, studies have also identified GEF effects on RhoA and CDC42, albeit to a less efficient extent [226], where TIAM1 operates as a potent oncogene. Two members of the miR-10 family (miR-10a and miR-10b) have been shown to function as tumor suppressors by directly targeting TIAM1 [391][392][393][394]. The expression of these two miRNAs were found to be significantly reduced in tumor tissue compared to the matched normal tissue [391,393,394].…”

Section: Mirna Targeting Of Rhogefsmentioning

confidence: 99%

“…Two members of the miR-10 family (miR-10a and miR-10b) have been shown to function as tumor suppressors by directly targeting TIAM1 [391][392][393][394]. The expression of these two miRNAs were found to be significantly reduced in tumor tissue compared to the matched normal tissue [391,393,394]. The stable expression of these two miRNAs inhibited Rac activation, cell growth, migration and invasion, as well as induced apoptosis by regulating TIAM1 expression.…”

Section: Mirna Targeting Of Rhogefsmentioning

confidence: 99%

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MicroRNA Regulation of the Small Rho GTPase Regulators—Complexities and Opportunities in Targeting Cancer Metastasis

Humphries

Wang

Yang

2020

Cancers

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The small Rho GTPases regulate important cellular processes that affect cancer metastasis, such as cell survival and proliferation, actin dynamics, adhesion, migration, invasion and transcriptional activation. The Rho GTPases function as molecular switches cycling between an active GTP-bound and inactive guanosine diphosphate (GDP)-bound conformation. It is known that Rho GTPase activities are mainly regulated by guanine nucleotide exchange factors (RhoGEFs), GTPase-activating proteins (RhoGAPs), GDP dissociation inhibitors (RhoGDIs) and guanine nucleotide exchange modifiers (GEMs). These Rho GTPase regulators are often dysregulated in cancer; however, the underlying mechanisms are not well understood. MicroRNAs (miRNAs), a large family of small non-coding RNAs that negatively regulate protein-coding gene expression, have been shown to play important roles in cancer metastasis. Recent studies showed that miRNAs are capable of directly targeting RhoGAPs, RhoGEFs, and RhoGDIs, and regulate the activities of Rho GTPases. This not only provides new evidence for the critical role of miRNA dysregulation in cancer metastasis, it also reveals novel mechanisms for Rho GTPase regulation. This review summarizes recent exciting findings showing that miRNAs play important roles in regulating Rho GTPase regulators (RhoGEFs, RhoGAPs, RhoGDIs), thus affecting Rho GTPase activities and cancer metastasis. The potential opportunities and challenges for targeting miRNAs and Rho GTPase regulators in treating cancer metastasis are also discussed. A comprehensive list of the currently validated miRNA-targeting of small Rho GTPase regulators is presented as a reference resource.

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“…Most mature miRNAs inhibit gene expression by cutting target messenger RNA(mRNAs) or inhibiting mRNAs’ translation by binding to the 3 ’-UTRs of mRNAs. (6) More and more reports have shown that miRNA plays an important role in the proliferation, apoptosis, invasion and migration of tumor cells. Abnormal expression of miRNA can be used for tumor classification, diagnosis and prognosis.…”

Section: Introductionmentioning

confidence: 99%

Microarray screening of differentially expressed genes after up-regulating miR-205 or down-regulating miR-141 in cervical cancer cells

Fang

Yao

2019

Preprint

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10 11 12 13 14 15 16 17 18 19 20 2 21 Microarray screening of differentially expressed genes after up-regulating miR-205 or 22 down-regulating miR-141 in cervical cancer cells 23 Abstract 24 Cervical cancer is one of the most common gynecological malignancies. However,studies 25 on the expression and molecular mechanism of miR-205 and miR-141 in CC are insufficient 26 recently. Expression profile microarray with 21329 Oligo DNA were used to detect the 27 expression of mRNAs in miR-205 up-regulated or miR-141 down-regulated HeLa and SiHa 28 cells and mRNAs in normal HeLa and SiHa cells. Gene Ontology (GO), Kyoto Encyclopedia 29 of Genes and Genomes (KEGG) pathway were performed to assess the potential pathways 30 of miR-205 in SiHa cell.Compared with normal HeLa cell, there were 38 differentially 31 expressed genes (DEGs) in miR-205 up-regulated HeLa cell. Nine were up-regulation genes 32 and 29 were down-regulation genes. There were 23 DEGs in miR-141 down-regulated HeLa 33 cell. One was up-regulated and 22 were down-regulated. Compared with normal SiHa cell, 34 there were 128 DEGs in miR-205 up-regulated SiHa cell. One hundred and three were up-35 regulation genes and 25 were down-regulation genes. There were 80 DEGs in miR-141 36 down-regulated SiHa cell. Forty two were up-regulation genes and 28 were down-regulation 37 genes. For miR-205 up-regulated SiHa cell, GO outcome showed that "ubiquitin-protein 38 ligase activity", "MAP kinase phosphatase activity", were the most enriched terms (P < 0.05). 39 And in KEGG analysis, "Cell cycle" was notably enriched, and Smad4 in this pathway was 40 up-regulated (P < 0.05). Expression profile microarray technology can effectively screen out 41 DEGs in cervical cancer cells after up-regulating miR-205 or down-regulating miR-141. 42 Which may enable us to understand the pathogenesis and lay an important foundation for 43 the prevention and treatment of cervical cancer. 44 Keywords: Gene expression profiling, cervical cancer, miRNA. 45 Introduction 3 46 Cervical cancer is one of the most common gynecological malignancies and the fourth 47 leading cause of cancer-related death worldwide. There were 527,600 new cases of cervical 48 cancer and 265,700 deaths worldwide in 2012.(1) It is the most common cancer of women in 49 many low-income countries.(2) Persistent infection of human papillomavirus (HPV) type 16 50 and 18 are the major risk factors for cervical cancer. In HPV high-risk cervical cancer cases, 51 HPV16 and 18 phenotypes account for 70%.(3) After HPV DNA integrated into the host DNA, 52 E6 and E7 genes are expressed. E6 induces the degradation of p53, stimulates telomerase 53 activity, and induces centrosome distortion and instability of the chromosome.(4) The binding 54 of E7 protein with human pRb and E2F transcription factor mediates cell transformation, 55 leading to the separation of pRb and E2F transcription factor and making cells enter S phase 56 of cell cycle early.(5) The occurrence of cervical cancer is a multi-factor, multi-stage and 57 multi-gene proce...

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miR-10b Downregulated by DNA Methylation Acts as a Tumor Suppressor in HPV-Positive Cervical Cancer via Targeting Tiam1

Cited by 27 publications

References 13 publications

Tiam1 high expression is associated with poor prognosis in solid cancers

Tiam1 high expression is associated with poor prognosis in solid cancers

MicroRNA Regulation of the Small Rho GTPase Regulators—Complexities and Opportunities in Targeting Cancer Metastasis

Microarray screening of differentially expressed genes after up-regulating miR-205 or down-regulating miR-141 in cervical cancer cells

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